Abstract-The aim of this study was to explore the effects of the renin inhibitor aliskiren in streptozotocin-diabetic TG(mRen-2)27 rats. Furthermore, we investigated in vitro the effect of aliskiren on the interactions between renin and the (pro)renin receptor and between aliskiren and prorenin. Aliskiren distributed extensively to the kidneys of normotensive (non)diabetic rats, localizing in the glomeruli and vessel walls after 2 hours exposure. In diabetic TG(mRen-2)27 rats, aliskiren (10 or 30 mg/kg per day, 10 weeks) lowered blood pressure, prevented albuminuria, and suppressed renal transforming growth factor-␤ and collagen I expression versus vehicle. Aliskiren reduced (pro)renin receptor expression in glomeruli, tubules, and cortical vessels compared to vehicle (in situ hybridization). In human mesangial cells, aliskiren (0.1 mol/L to 10 mol/L) did not inhibit binding of 125 I-renin to the (pro)renin receptor, nor did it alter the activation of extracellular signal-regulated kinase 1/2 by renin (20 nmol/L) preincubated with aliskiren (100 nmol/L) or affect gene expression of the (pro)renin receptor. Evidence was obtained that aliskiren binds to the active site of prorenin. The above results demonstrate the antihypertensive and renoprotective effects of aliskiren in experimental diabetic nephropathy. The evidence that aliskiren can reduce in vivo gene expression for the (pro)renin receptor and that it may block prorenin-induced angiotensin generation supports the need for additional work to reveal the mechanism of the observed renoprotection by this renin inhibitor. Key Words: aliskiren Ⅲ renin inhibitor Ⅲ TG(mRen-2)rat Ⅲ diabetic nephropathy Ⅲ (pro)renin receptor A central role for the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of diabetic nephropathy (DN) is widely accepted, based largely on the attenuation of DN by angiotensin (Ang) converting enzyme inhibitors (ACEi) 1 and Ang II receptor blockers (ARB). 2 However, these agents do not halt renal decline, possibly because of insufficient suppression of the intrarenal RAAS. Theoretically, agents that more effectively suppress the RAAS should confer improved tissue protection over current treatments for DN. Renin inhibitors, by acting at the point of activation of the RAAS cascade, may represent such agents. Aliskiren is a potent inhibitor of human renin; it lowers blood pressure (BP) in patients with mild-moderate hypertension 3,4 and shows cardiorenal protection in hypertensive double transgenic rats expressing human genes for renin and angiotensinogen. 5

No abstract

Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial.

By carefully and systematically performing Green-Kubo equilibrium molecular dynamics simulations, we report that the thermal conductivity (κ) of Si nanowires (NWs) does not diverge but converges and increases steeply when NW diameter (D) becomes extremely small (dκ/dD < 0), a long debate of one-dimensional heat conduction in history. The κ of the thinnest possible Si NWs reaches a superhigh level that is as large as more than 1 order of magnitude higher than its bulk counterpart. The abnormality is explained in terms of the dominant normal (N) process (energy and momentum conservation) of low frequency acoustic phonons that induces hydrodynamic phonon flow in the Si NWs without being scattered. With D increasing, the downward shift of optical phonons triggers strong Umklapp (U) scattering with acoustic phonons and attenuates the N process, leading to the regime of phonon boundary scattering (dκ/dD < 0). The two competing mechanisms result in nonmonotonic diameter dependence of κ with minima at critical diameter of 2-3 nm. Our results unambiguously demonstrate the converged κ and the clear trend of κ ∼ D for extremely thin Si NWs by fully elucidating the competition between the hydrodynamic phonon flow and phonon boundary scattering.

No abstract

We compared the temperature dependence of spin lifetime in n-Ge characterized from three-terminal (3T) and four-terminal (4T) Hanle measurements using single-crystalline Fe/MgO/n-Ge tunnel junctions. The bias conditions of the two schemes were chosen to be about the same in order to compare the spin lifetimes (τ 3T and τ 4T ). The temperature dependences of τ 3T and τ 4T behave in a very similar way at the low temperature region (T 10 K), and both τ 3T and τ 4T decrease as the temperature increases, which is consistent with the dominating Elliot-Yafet spin relaxation mechanism in bulk Ge. However, when the temperature is higher than 10 K, τ 4T is longer than τ 3T , which may be explained by the fact that 3T Hanle measurements are more easily affected by additional scattering effects caused by the accompanied charge current and electric field in the 3T geometry.

No abstract

Phase-change materials (crystalline at low temperatures and partial-crystalline partial-liquid state at high temperatures) are widely used as thermoelectric converters and battery electrodes. Here, we report the underlying mechanisms driving the thermal transport of the liquid component, and the thermal conductivity contributions from phonons, vibrations with extremely short mean free path, liquid and lattice-liquid interactions in phase-changed Li2S. In the crystalline state (T ≤ 1000 K), the temperature dependent thermal conductivity manifests two different behaviors, i.e., a typical trend of 1/T below 800 K and an even faster decrease between 800 and 1000 K. For the partial-crystalline partial-liquid Li2S when T ≥ 1100 K, the contributions of liquid and lattice-liquid interactions increase significantly due to the fluidization of Li ions, and the vibrations with extremely short mean free path, presumably assimilated to diffusons, can contribute up to 46% of the total thermal conductivity at T = 1300 K.